The MLH1 variants p.Arg265Cys and p.Lys618Ala affect protein stability while p.Leu749Gln affects heterodimer formation.
Hum Mutat
; 29(2): 332, 2008 Feb.
Article
em En
| MEDLINE
| ID: mdl-18205192
ABSTRACT
Germline mutations in the mismatch repair genes lead to the Lynch syndrome/ HNPCC, and genetic testing is offered to identify individuals at risk of developing this disease. About a third of all genetic alterations detected in the mismatch repair gene MutL homolog 1 (MLH1) are missense variants. The majority of these variants are of equivocal clinical significance. In this report, we investigate the molecular basis of the pathogenicity of three missense variants localized to distinct functional domains. Our results demonstrate that the MLH1 variants p.Arg265Cys (c.793C>T) and p.Lys618Ala (c.1852_1853AA>GC) significantly decrease the stability of the protein, while another missense variant p.Leu749Gln (c.2246T>A) is able to compromise heterodimerization of the MLH1-PMS2 complex.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Substituição de Aminoácidos
/
Proteínas Adaptadoras de Transdução de Sinal
/
Proteínas Mutantes
/
Aminoácidos
Limite:
Humans
Idioma:
En
Revista:
Hum Mutat
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Canadá